Xiaorong Yang1,2, Chen Suo3, Tongchao Zhang4, Xiaolin Yin4, Jinyu Man4, Ziyu Yuan5, Jingru Yu6, Li Jin5,7, Xingdong Chen8,9, Ming Lu10,11,12, Weimin Ye5,6,13. 1. Clinical Epidemiology Unit, Qilu Hospital of Shandong University, 107 Wenhuaxi Road, Jinan, 250012, Shandong, China. 2. Clinical Research Center of Shandong University, Qilu Hospital of Shandong University, Jinan, China. 3. Department of Epidemiology and Health Statistics, School of Public Health, Fudan University, Shanghai, China. 4. Department of Epidemiology and Health Statistics, School of Public Health, Shandong University, Jinan, China. 5. Fudan University Taizhou Institute of Health Sciences, Taizhou, China. 6. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. 7. State Key Laboratory of Genetic Engineering, Human Phenome Institute, and School of Life Sciences, Fudan University, Songhu Road 2005, Shanghai, 200438, China. 8. Fudan University Taizhou Institute of Health Sciences, Taizhou, China. xingdongchen@fudan.edu.cn. 9. State Key Laboratory of Genetic Engineering, Human Phenome Institute, and School of Life Sciences, Fudan University, Songhu Road 2005, Shanghai, 200438, China. xingdongchen@fudan.edu.cn. 10. Clinical Epidemiology Unit, Qilu Hospital of Shandong University, 107 Wenhuaxi Road, Jinan, 250012, Shandong, China. lvming@sdu.edu.cn. 11. Clinical Research Center of Shandong University, Qilu Hospital of Shandong University, Jinan, China. lvming@sdu.edu.cn. 12. Fudan University Taizhou Institute of Health Sciences, Taizhou, China. lvming@sdu.edu.cn. 13. Department of Epidemiology and Health Statistics & Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China.
Abstract
BACKGROUND: Early diagnosis of esophageal squamous cell carcinoma (ESCC) remains a challenge due to the lack of specific blood biomarkers. We aimed to develop a serum multi-protein signature for the early detection of ESCC. METHODS: We selected 70 healthy controls, 30 precancerous patients, 60 stage I patients, 70 stage II patients and 70 stage III/IV ESCC patients from a completed ESCC case-control study in a high-risk area of China. Olink Multiplex Oncology II targeted proteomics panel was used to simultaneously detect the levels of 92 cancer-related proteins in serum using proximity extension assay. RESULTS: We found that 10 upregulated and 13 downregulated protein biomarkers in serum could distinguish the early-stage ESCC from healthy controls, which were validated by the significant dose-response relationships with ESCC pathological progression. Applying least absolute shrinkage and selection operator (LASSO) regression and backward elimination algorithm, ANXA1 (annexin A1), hK8 (kallikrein-8), hK14 (kallikrein-14), VIM (vimentin), and RSPO3 (R-spondin-3) were kept in the final model to discriminate early ESCC cases from healthy controls with an area under curve (AUC) of 0.936 (95% confidence interval: 0.899 ~ 0.973). The average accuracy rates of the five-protein classifier were 0.861 and 0.825 in training and test data by five-fold cross-validation. CONCLUSIONS: Our study suggested that a combination of ANXA1, hK8, hK14, VIM and RSPO3 serum proteins could be considered as a potential tool for screening and early diagnosis of ESCC, especially with the establishment of a three-level hierarchical screening strategy for ESCC control.
BACKGROUND: Early diagnosis of esophageal squamous cell carcinoma (ESCC) remains a challenge due to the lack of specific blood biomarkers. We aimed to develop a serum multi-protein signature for the early detection of ESCC. METHODS: We selected 70 healthy controls, 30 precancerous patients, 60 stage I patients, 70 stage II patients and 70 stage III/IV ESCC patients from a completed ESCC case-control study in a high-risk area of China. Olink Multiplex Oncology II targeted proteomics panel was used to simultaneously detect the levels of 92 cancer-related proteins in serum using proximity extension assay. RESULTS: We found that 10 upregulated and 13 downregulated protein biomarkers in serum could distinguish the early-stage ESCC from healthy controls, which were validated by the significant dose-response relationships with ESCC pathological progression. Applying least absolute shrinkage and selection operator (LASSO) regression and backward elimination algorithm, ANXA1 (annexin A1), hK8 (kallikrein-8), hK14 (kallikrein-14), VIM (vimentin), and RSPO3 (R-spondin-3) were kept in the final model to discriminate early ESCC cases from healthy controls with an area under curve (AUC) of 0.936 (95% confidence interval: 0.899 ~ 0.973). The average accuracy rates of the five-protein classifier were 0.861 and 0.825 in training and test data by five-fold cross-validation. CONCLUSIONS: Our study suggested that a combination of ANXA1, hK8, hK14, VIM and RSPO3 serum proteins could be considered as a potential tool for screening and early diagnosis of ESCC, especially with the establishment of a three-level hierarchical screening strategy for ESCC control.
Authors: Björn L D M Brücher; Yan Li; Philipp Schnabel; Martin Daumer; Timothy J Wallace; Rainer Kube; Bruno Zilberstein; Scott Steele; Jan L A Voskuil; Ijaz S Jamall Journal: Clin Transl Med Date: 2016-04-06
Authors: Blendi Ura; Valeria Capaci; Michelangelo Aloisio; Giovanni Di Lorenzo; Federico Romano; Giuseppe Ricci; Lorenzo Monasta Journal: Biomedicines Date: 2022-08-02